Previous studies have shown that spinosin was implicated in the modulation of sedation and hypnosis, while its effects on learning and memory deficits were rarely reported. The aim of this study is to investigate the effects of spinosin on the improvement of cognitive impairment in model mice with A...
Previous studies have shown that spinosin was implicated in the modulation of sedation and hypnosis, while its effects on learning and memory deficits were rarely reported. The aim of this study is to investigate the effects of spinosin on the improvement of cognitive impairment in model mice with Alzheimer's disease (AD) induced by $A{\beta}_{1-42}$ and determine the underlying mechanism. Spontaneous locomotion assessment and Morris water maze test were performed to investigate the impact of spinosin on behavioral activities, and the pathological changes were assayed by biochemical analyses and histological assay. After 7 days of intracerebroventricular (ICV) administration of spinosin ($100{\mu}g/kg/day$), the cognitive impairment of mice induced by $A{\beta}_{1-42}$ was significantly attenuated. Moreover, spinosin treatment effectively decreased the level of malondialdehyde (MDA) and $A{\beta}_{1-42}$ accumulation in hippocampus. $A{\beta}_{1-42}$ induced alterations in the expression of brain derived neurotrophic factor (BDNF) and B-cell lymphoma-2 (Bcl-2), as well as inflammatory response in brain were also reversed by spinosin treatment. These results indicated that the ameliorating effect of spinosin on cognitive impairment might be mediated through the regulation of oxidative stress, inflammatory process, apoptotic program and neurotrophic factor expression,suggesting that spinosin might be beneficial to treat learning and memory deficits in patients with AD via multi-targets.
Previous studies have shown that spinosin was implicated in the modulation of sedation and hypnosis, while its effects on learning and memory deficits were rarely reported. The aim of this study is to investigate the effects of spinosin on the improvement of cognitive impairment in model mice with Alzheimer's disease (AD) induced by $A{\beta}_{1-42}$ and determine the underlying mechanism. Spontaneous locomotion assessment and Morris water maze test were performed to investigate the impact of spinosin on behavioral activities, and the pathological changes were assayed by biochemical analyses and histological assay. After 7 days of intracerebroventricular (ICV) administration of spinosin ($100{\mu}g/kg/day$), the cognitive impairment of mice induced by $A{\beta}_{1-42}$ was significantly attenuated. Moreover, spinosin treatment effectively decreased the level of malondialdehyde (MDA) and $A{\beta}_{1-42}$ accumulation in hippocampus. $A{\beta}_{1-42}$ induced alterations in the expression of brain derived neurotrophic factor (BDNF) and B-cell lymphoma-2 (Bcl-2), as well as inflammatory response in brain were also reversed by spinosin treatment. These results indicated that the ameliorating effect of spinosin on cognitive impairment might be mediated through the regulation of oxidative stress, inflammatory process, apoptotic program and neurotrophic factor expression,suggesting that spinosin might be beneficial to treat learning and memory deficits in patients with AD via multi-targets.
* AI 자동 식별 결과로 적합하지 않은 문장이 있을 수 있으니, 이용에 유의하시기 바랍니다.
제안 방법
For the long-term memory evaluated by Morris maze test, mice with Aβ1-42 injection spent longer time searching for the hidden platform (latency time) than the control group during the five days training sessions.
데이터처리
The significances among different groups were determined using SPSS 19.0 (IBM Corp., New York, NY) where statistical significance were assessed by one-way analysis of variance (ANOVA) followed by Tukey’s multiple comparison test, p<0.05 was considered statistically significant.
성능/효과
In conclusion, in addition to previously reported targets of spinosin, neuroprotective effects of spinosin were found through the regulation of oxidative stress, Aβ1-42 accumulation, as well as apoptotic program in brain.
Our results showed an increased level of IL-6 in hippocampus of mice after Aβ1-42 injection, while the administration of spinosin decreased IL-6 level in the hippocampus (Fig. 6).
Our results showed that spinosin significantly attenuated the up-regulation of MDA in hippocampus induced by ICV injection of Aβ1-42.
The Aβ1-42 levels in hippocampus homogenate were evaluated, and the results showed that ICV injection of Aβ1-42 significantly increased the Aβ1-42 level in the hippocampus of mice in model group (p<0.01).
참고문헌 (33)
Ahmad M Saleem S Ahmad AS Yousuf S Ansari MA Khan MB Ishrat T Chaturvedi RK Agrawal AK Islam F 2005 Ginkgo biloba affords dose-dependent protection against 6-hydroxydopamine-induced Parkinsonism in rats: neurobehavioural, neurochemical and immunohistochemical evidences J. Neurochem 93 94 104 10.1111/j.1471-4159.2005.03000.x 15773909
Almeida RD Manadas BJ Melo CV Gomes JR Mendes CS Grãos MM Carvalho RF Carvalho AP Duarte CB 2005 Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways Cell Death Differ 12 1329 1343 10.1038/sj.cdd.4401662 15905876
Butterfield DA Stadtman ER 1997 Protein oxidation processes in aging brain Adv. Cell Aging Gerontol 2 161 191 10.1016/S1566-3124(08)60057-7
Chu YF Chang WH Black RM Liu JR Sompol P Chen Y 2012 Crude caffeine reduces memory impairment and amyloid β 1–42 levels in an Alzheimer’s mouse model Food Chem 135 2095 2102 10.1016/j.foodchem.2012.04.148 22953961
Drummond SPA Brown GG 2001 The effects of total sleep deprivation on cerebral responses to cognitive performance Neuropsychopharmacology 25 S68 S73 10.1016/S0893-133X(01)00325-6 11682277
Graves LA Heller EA Pack AI Abel T 2003 Sleep deprivation selectively impairs memory consolidation for contextual fear conditioning Learn. Mem 10 168 176 10.1101/lm.48803 202307 --> 12773581
Hardy J Selkoe DJ 2002 The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics Science 297 353 356 10.1126/science.1072994 12130773
Ianiski FR Alves CB Souza ACG Pinton S Roman SS Rhoden CRB Alves MP Luchese C 2012 Protective effect of meloxicam-loaded nanocapsules against amyloid-β peptide-induced damage in mice Behav. Brain Res 230 100 107 10.1016/j.bbr.2012.01.055 22342489
Jiang JG Huang XJ Chen J Lin QS 2007 Comparison of the sedative and hypnotic effects of flavonoids, saponins, and polysaccharides extracted from Semen Ziziphus jujube Nat. Prod. Res 21 310 320 10.1080/14786410701192827 17479419
Jung IH Lee HE Park SJ Ahn YJ Kwon G Woo H Lee SY Kim JS Jo YW Jang DS Kang SS Ryu JH 2014 Ameliorating effect of spinosin, a C-glycoside flavonoid, on scopolamine-induced memory impairment in mice Pharmacol. Biochem. Behav 120 88 94 10.1016/j.pbb.2014.02.015 24582850
Ko SY Lee HE Park SJ Jeon SJ Kim B Gao Q Jang DS Ryu JH 2015 Spinosin, a C-glucosylflavone, from Zizyphus jujuba var. spinosa ameliorates Abeta 1–42 oligomer-induced memory impairment in mice Biomol. Ther. (Seoul) 23 156 164 10.4062/biomolther.2014.110 25767684
Kowalska A 2004 The beta-amyloid cascade hypothesis: a sequence of events leading to neurodegeneration in Alzheimer’s disease Neurol. Neurochir. Pol 38 405 412 15565529
Lee Y Jeon SJ Lee HE Jung IH Jo YW Lee S Cheong JH Jang DS Ryu JH 2016 Spinosin, a C-glycoside flavonoid, enhances cognitive performance and adult hippocampal neurogenesis in mice Pharmacol. Biochem. Behav 145 9 16 10.1016/j.pbb.2016.03.007 26997033
Mao X Liao Z Guo L Xu X Wu B Xu M Zhao X Bi K Jia Y 2015 Schisandrin C ameliorates learning and memory deficits by Abeta 1–42 -induced oxidative stress and neurotoxicity in mice Phytother. Res 29 1373 1380 10.1002/ptr.5390 26074330
Nagele RG Wegiel J Venkataraman V Wang KC Wegiel J 2004 Contribution of glial cells to the development of amyloid plaques in Alzheimer’s disease Neurobiol. Aging 25 663 674 10.1016/j.neurobiolaging.2004.01.007 15172746
Numakawa T Suzuki S Kumamaru E Adachi N Richards M Kunugi H 2010 BDNF function and intracellular signaling in neurons Histol. Histopathol 25 237 258 20017110
Palop JJ Mucke L 2010 Amyloid-beta induced neuronal dysfunction in Alzheimer’s disease: from synapses toward neural networks Nat. Neurosci 13 812 818 10.1038/nn.2583 3072750 --> 20581818
Pauwels K Williams TL Morris KL Jonckheere W Vandersteen A Kelly G Schymkowitz JS Rousseau F Pastore A Serpell LC Broersen K 2012 Structural basis for increased toxicity of pathological aβ42: aβ40 ratios in Alzheimer disease J. Biol. Chem 287 5650 5660 10.1074/jbc.M111.264473 22157754
Wang LE Bai YJ Shi XR Cui XY Cui SY Zhang F Zhang QY Zhao YY Zhang YH 2008 Spinosin, a Cglycoside flavonoid from semen Zizhiphi Spinozae, potentiated pentobarbital-induced sleep via the serotonergic system Pharmacol. Biochem. Behav 90 399 403 10.1016/j.pbb.2008.03.022 18466960
Wang LE Cui XY Cui SY Cao JX Zhang J Zhang YH Zhang QY Bai YJ Zhao YY 2010 Potentiating effect of spinosin, a C-glycoside flavonoid of Semen Ziziphi spinosae, on pentobarbital-induced sleep may be related to postsynaptic 5-HT1A receptors Phytomedicine 17 404 409 10.1016/j.phymed.2010.01.014 20171860
Wu L Tong T Wan S Yan T Ren F Bi K Jia Y 2017 Protective effects of puerarin against Aβ 1–42 -induced learning and memoryimpairments in mice Planta Med 83 224 231 27420352
Yoon SS Jo SA 2012 Mechanisms of Amyloid-β peptide clearance: potential therapeutic targets for Alzheimer’s disease Biomol. Ther. (Seoul) 20 245 255 10.4062/biomolther.2012.20.3.245 24130920
You ZL Xia Q Liang FR Tang YJ Xu CL Huang J Zhao L Zhang WZ He JJ 2010 Effects on the expression of GABAA receptor subunits by jujuboside A treatment in rat hippocampal neurons J. Ethnopharmacol 128 419 423 10.1016/j.jep.2010.01.034 20083184
Zhang J Zhen YF Pu-Bu-Ci-Ren Song LG Kong W. N. Shao T. M. Li X. Chai XQ 2013 Salidroside attenuates beta amyloid-induced cognitive deficits via modulating oxidative stress and inflammatory mediators in rat hippocampus Behav. Brain. Res 244 70 81 10.1016/j.bbr.2013.01.037 23396166
Ziech D Franco R Georgakilas AG Georgakila S MalamouMitsi V Schoneveld O Pappa A Panayiotidis MI 2010 The role of reactive oxygen species and oxidative stress in environmental carcinogenesis and biomarker development Chem. Biol. Interact 188 334 339 10.1016/j.cbi.2010.07.010 20637748
※ AI-Helper는 부적절한 답변을 할 수 있습니다.